CircRNA circBACH1 facilitates hepatitis
B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis
Na Du1*, Kailin Li1*, Yu Wang2, Bo Song1, Xuan Zhou1 and Shaoqiong Duan1
1Department of Infectious Disease and 2Department of Cardiology, Suizhou Central Hospital Affiliated to Hubei Medical College, Suizhou, China
*These authors contributed equally to this paper
Corresponding Author: Shaoqiong Duan, Department of Infectious Disease, Suizhou Central Hospital Affiliated to Hubei Medical College, No. 8, Wendi Avenue, High-tech Zone, Zengdu District, Suizhou 441300, China. e-mail: duanshaoqiong1983@163.com
Summary. Background. Hepatitis B virus (HBV) is a top contributor to hepatoma. Circular RNAs (circRNAs) have been elucidated to have a close connection with HBV-induced hepatoma. This study aimed to explore the role of circRNA BTB domain and CNC homolog 1 (circBACH1) in HBV replication and hepatoma progression, as well as the potential mechanistic pathway.
Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to assess the expression of circBACH1, microRNA (miR)-200a-3p, and mitogen-activated protein kinase kinase kinase 2 (MAP3K2). HBV replication was determined by enzyme-linked immunosorbent assay (ELISA) and qRT-PCR assay. Cell viability and clonogenicity were detected via Cell Counting Kit-8 (CCK-8) assay and colony formation assay, respectively. Cell metastasis was examined by Transwell assay and wound healing assay. Annexing-V/PI staining was employed to monitor cell apoptosis using flow cytometry. Levels of MAP3K2, proliferation- and apoptosis-related proteins were analyzed by Western blotting. Target interaction between miR-200a-3p and circBACH1 or MAP3K2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circBACH1 in vivo was investigated by xenograft model assay.
Results. Expression of circBACH1 and MAP3K2 was increased, while miR-200a-3p expression was decreased in HCC tissues and HBV-transfected hepatoma cells. Depletion of circBACH1 or miR-200a-3p overexpression impeded HBV replication, proliferation, and metastasis in HBV-transfected hepatoma cells. CircBACH1 was able to regulate MAP3K2 expression by sponging miR-200a-3p. CircBACH1 regulated HBV replication and hepatoma progression through the miR-200a-3p/MAP3K2 pathway. Moreover, circBACH1 deficiency hampered tumor growth in vivo.
Conclusion. CircBACH1 knockdown had inhibitory effects on HBV replication and hepatoma progression, at least partly by modulating the miR-200a-3p/MAP3K2 axis. Histol Histopathol 37, 863-877 (2022)
Key words: Hepatoma, HBV replication, circBACH1, miR-200a-3p, MAP3K2
DOI: 10.14670/HH-18-452
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©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
